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Molecular Genetics & Genomic Medicine Volume 2 Issue 4 is Published!

July 15, 2014

Molecular Genetics & Genomic Medicine has now published its next issue. Editor-in-Chief: Max Muenke introduces his editorial highlights: “This issue includes an Invited Commentary on the genomics and epigenomics of substance use disorders and also features the third article in our series, “Genetics and Genomic Medicine around the World”, this month focusing on Brazil. Highlights of the issue include the articles, “Telomere Length, Family History and Paternal Age in Schizophrenia“, “Association of the c.385C>A (p.Pro129Thr) Polymorphism of the Fatty Acid Amide Hydrolase Gene with Anorexia Nervosa in the Japanese Population”, and “46,XY Disorder of Sexual Development Resulting from a Novel Monoallelic Mutation (p.Ser31Phe) in the Steroid 5α-Reductase Type-2 (SRD5A2) Gene”.

Telomere length, family history, and paternal age in schizophrenia by Dolores Malaspina, Roberta Dracxler, Julie Walsh-Messinger, Susan Harlap, Raymond R. Goetz, David Keefe and Mary C. Perrin.
Abstract: Leukocyte telomere length (LTL) is longer in association with advanced paternal age, but this association has not been examined along with family history (FH) in schizophrenia. LTL was measured by PCR and compared across cases and controls as part of a study to examine the characteristics of paternal age related schizophrenia. The 53 schizophrenia cases had similar mean LTL as 20 controls, although cases were significantly older than controls and overwhelmingly smoked cigarettes. Multivariate analyses showed that a FH of schizophrenia was associated with longer LTL in both male and female cases. Later paternal age was also related to longer LTL in male cases, but with shorter LTL in female cases. Male cases with older fathers and a FH had the longest LTL. The genetic architecture associated with a familial risk for schizophrenia may include pathways that lengthen LTL. Paternal aging conferred an additional increase in LTL lengthening in male cases, but reduced LTL in female cases. The gender difference in LTL for paternal aging is consistent with the severe illness features reported for female cases with older fathers and could implicate epigenetic alterations in the paternal X chromosomal region with advanced paternal age in association with the risk for schizophrenia.

Association of the c.385C>A (p.Pro129Thr) Polymorphism of the Fatty Acid Amide Hydrolase Gene with Anorexia Nervosa in the Japanese Population by Tetsuya Ando, Naho Tamura, Takashi Mera, Chihiro Morita, Michiko Takei, Chiemi Nakamoto, Masanori Koide, Mari Hotta, Tetsuro Naruo, Keisuke Kawai, Toshihiro Nakahara, Chikara Yamaguchi, Toshihiko Nagata, Kazuyoshi Ookuma, Yuri Okamoto, Takao Yamanaka, Nobuo Kiriike, Yuhei Ichimaru, Toshio Ishikawa, Gen Komaki and The Japanese Genetic Research Group For Eating Disorders.
Abstract: The functional c.385C>A single-nucleotide polymorphism (SNP) in the fatty acid amide hydrolase (FAAH) gene, one of the major degrading enzymes of endocannabinoids, is reportedly associated with anorexia nervosa (AN). We genotyped the c.385C>A SNP (rs324420) in 762 lifetime AN and 605 control participants in Japan. There were significant differences in the genotype and allele frequencies of c.385C>A between the AN and control groups. The minor 385A allele was less frequent in the AN participants than in the controls (allele-wise, odds ratio = 0.799, 95% confidence interval [CI] 0.653–0.976, P = 0.028). When the cases were subdivided into lifetime restricting subtype AN and AN with a history of binge eating or purging, only the restricting AN group exhibited a significant association (allele-wise, odds ratio = 0.717, 95% CI 0.557–0.922, P = 0.0094). Our results suggest that having the minor 385A allele of the FAAH gene may be protective against AN, especially restricting AN. This finding supports the possible role of the endocannabinoid system in susceptibility to AN.

46,XY Disorder of Sexual Development Resulting from a Novel Monoallelic Mutation (p.Ser31Phe) in the Steroid 5α-Reductase Type-2 (SRD5A2) Gene by Bertha Chávez, Luis Ramos, Rita Gómez and Felipe Vilchis.
Abstract: Inactivating mutations of the 5α-steroid reductase type-2 (SRD5A2) gene result in a broad spectrum of masculinization defects, ranging from a male phenotype with hypospadias to a female phenotype with Wolffian structures. Molecular studies of the SRD5A2 revealed a new heterozygous gene variant within the coding region that results in phenotypic expression. A c.92C>T transition changing serine to phenylalanine at codon 31 of exon 1 (p.Ser31Phe) was identified in a patient with 46,XY disorder of sexual development who displayed glandular hypospadias with micropenis and bilateral cryptorchidism. The restoration of the p.Ser31Phe mutation by site-directed mutagenesis and transient expression assays using cultured HEK-293 cells showed that this novel substitution does not abolish but does deregulate the catalytic efficiency of the enzyme. Thus, the maximum velocity (Vmax) value was higher for the mutant enzyme (22.5 ± 6.9 nmol DHT mg protein−1 h−1) than for the wild-type enzyme (9.8 ± 2.0 nmol DHT mg protein−1 h−1). Increased in vitro activity of the p.Ser31Phe mutant suggested an activating effect. This case provides evidence that heterozygous missense mutations in SRD5A2 may induce the abnormal development of male external genitalia..

The journal also publishes Genetics and Genomic Medicine around the World. Below is the second article of this type, this month focusing on Brazil.

Genetics and genomics in Brazil: a promising future” by Maria Rita Passos-Bueno, Debora Bertola, Dafne Dain Gandelman Horovitz, Victor Evangelista de Faria Ferraz and Luciano Abreu Brito.

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